Fiber shaft-chimeric adenovirus vectors lacking the KKTK motif efficiently infect liver cells in vivo.

ABSTRACT: The molecular mechanisms governing the infectivity of adenovirus (Ad) toward specific cell and tissue types in vivo remain poorly understood. The direct Ad binding to hepatic heparan sulfate proteoglycans via the KKTK motif within the fiber shaft domain was suggested to be the major mechanism of Ad liver cell infection in vivo. Here, we describe the generation and in vitro and in vivo infectivity studies of Ad5-based vectors possessing long Ad31- or Ad41-derived fiber shaft domains, which lack the KKTK motif. We found that all the critical early steps of Ad infection, including attachment to the cellular receptor, internalization, and virus genome transfer into the nucleus, occurred with similar levels of efficiency for fiber shaft-chimeric vectors and unmodified Ad5. Upon intravenous deli

SUBMITTER: Di Paolo NC 

PROVIDER: S-EPMC2168974 | biostudies-literature | 2007 Nov

REPOSITORIES: biostudies-literature